Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
Clin Cancer Res. 2011 Jun 1;17(11):3742-50. doi: 10.1158/1078-0432.CCR-10-3405. Epub 2011 Mar 8.
An assay for the single-nucleotide polymorphism (SNP), rs61764370, has recently been commercially marketed as a clinical test to aid ovarian cancer risk evaluation in women with family histories of the disease. rs67164370 is in a 3'-UTR miRNA binding site of the KRAS oncogene and is a candidate for epithelial ovarian cancer (EOC) susceptibility. However, only one published article, analyzing fewer than 1,000 subjects in total, has examined this association.
Risk association was evaluated in 8,669 cases of invasive EOC and 10,012 controls from 19 studies participating in the Ovarian Cancer Association Consortium, and in 683 cases and 2,044 controls carrying BRCA1 mutations from studies in the Consortium of Investigators of Modifiers of BRCA1/2. Prognosis association was also examined in a subset of five studies with progression-free survival (PFS) data and 18 studies with all-cause mortality data.
No evidence of association was observed between genotype and risk of unselected EOC (OR = 1.02, 95% CI: 0.95-1.10), serous EOC (OR = 1.08, 95% CI: 0.98-1.18), familial EOC (OR = 1.09, 95% CI: 0.78-1.54), or among women carrying deleterious mutations in BRCA1 (OR = 1.09, 95% CI: 0.88-1.36). There was little evidence for association with survival time among unselected cases (HR = 1.10, 95% CI: 0.99-1.22), among serous cases (HR = 1.12, 95% CI = 0.99-1.28), or with PFS in 540 cases treated with carboplatin and paclitaxel (HR = 1.18, 95% CI: 0.93-1.52).
These data exclude the possibility of an association between rs61764370 and a clinically significant risk of ovarian cancer or of familial ovarian cancer. Use of this SNP for ovarian cancer clinical risk prediction, therefore, seems unwarranted.
最近，一种用于检测单核苷酸多态性（SNP）rs61764370 的检测方法已被商业化，用于帮助有卵巢癌家族史的女性评估卵巢癌风险。rs67164370 位于 KRAS 癌基因的 3'-UTR miRNA 结合位点，是上皮性卵巢癌（EOC）易感性的候选基因。然而，仅有一篇已发表的文章对这一关联进行了分析，该文章总共分析了不到 1000 名受试者。
我们评估了 19 项研究中的卵巢癌协会联盟（Ovarian Cancer Association Consortium）中 8669 例侵袭性 EOC 病例和 10012 例对照，以及 683 例携带 BRCA1 突变的病例和 2044 例对照。在包含无进展生存期（PFS）数据的 5 项研究和包含全因死亡率数据的 18 项研究中，还检测了预后关联。
在未选择的 EOC（OR = 1.02，95%CI：0.95-1.10）、浆液性 EOC（OR = 1.08，95%CI：0.98-1.18）、家族性 EOC（OR = 1.09，95%CI：0.78-1.54）或携带 BRCA1 有害突变的女性中，均未观察到基因型与风险之间存在关联（OR = 1.09，95%CI：0.88-1.36）。在未选择的病例中，与生存时间几乎没有关联（HR = 1.10，95%CI：0.99-1.22），在浆液性病例中（HR = 1.12，95%CI = 0.99-1.28），或在接受卡铂和紫杉醇治疗的 540 例患者的 PFS 中（HR = 1.18，95%CI：0.93-1.52）。
这些数据排除了 rs61764370 与卵巢癌临床显著风险或家族性卵巢癌之间存在关联的可能性。因此，使用该 SNP 进行卵巢癌临床风险预测似乎是没有必要的。
